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Biology LibreTexts

35.2E: Synaptic Plasticity

  • Page ID
    13873
  • LEARNING OBJECTIVES

    • Distinguish between long-term potentiation and long-term depression

    Synaptic plasticity is the strengthening or weakening of synapses over time in response to increases or decreases in their activity. Plastic change also results from the alteration of the number of receptors located on a synapse. Synaptic plasticity is the basis of learning and memory, enabling a flexible, functioning nervous system. Synaptic plasticity can be either short-term (synaptic enhancement or synaptic depression) or long-term. Two processes in particular, long-term potentiation (LTP) and long-term depression (LTD), are important forms of synaptic plasticity that occur in synapses in the hippocampus: a brain region involved in storing memories.

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    Long-term potentiation and depression: Calcium entry through postsynaptic NMDA receptors can initiate two different forms of synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). LTP arises when a single synapse is repeatedly stimulated. This stimulation causes a calcium- and CaMKII-dependent cellular cascade, which results in the insertion of more AMPA receptors into the postsynaptic membrane. The next time glutamate is released from the presynaptic cell, it will bind to both NMDA and the newly-inserted AMPA receptors, thus depolarizing the membrane more efficiently. LTD occurs when few glutamate molecules bind to NMDA receptors at a synapse (due to a low firing rate of the presynaptic neuron). The calcium that does flow through NMDA receptors initiates a different calcineurin and protein phosphatase 1-dependent cascade, which results in the endocytosis of AMPA receptors. This makes the postsynaptic neuron less responsive to glutamate released from the presynaptic neuron.

    Short-term Synaptic Enhancement and Depression

    Short-term synaptic plasticity acts on a timescale of tens of milliseconds to a few minutes. Short-term synaptic enhancement results from more synaptic terminals releasing transmitters in response to presynaptic action potentials. Synapses will strengthen for a short time because of either an increase in size of the readily- releasable pool of packaged transmitter or an increase in the amount of packaged transmitter released in response to each action potential. Depletion of these readily-releasable vesicles causes synaptic fatigue. Short-term synaptic depression can also arise from post-synaptic processes and from feedback activation of presynaptic receptors.

    Long-term Potentiation (LTP)

    Long-term potentiation (LTP) is a persistent strengthening of a synaptic connection, which can last for minutes or hours. LTP is based on the Hebbian principle: “cells that fire together wire together. ” There are various mechanisms, none fully understood, behind the synaptic strengthening seen with LTP.

    One known mechanism involves a type of postsynaptic glutamate receptor: NMDA (N-Methyl-D-aspartate) receptors. These receptors are normally blocked by magnesium ions. However, when the postsynaptic neuron is depolarized by multiple presynaptic inputs in quick succession (either from one neuron or multiple neurons), the magnesium ions are forced out and Ca2+ ions pass into the postsynaptic cell. Next, Ca2+ ions entering the cell initiate a signaling cascade that causes a different type of glutamate receptor, AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, to be inserted into the postsynaptic membrane. Activated AMPA receptors allow positive ions to enter the cell.

    Therefore, the next time glutamate is released from the presynaptic membrane, it will have a larger excitatory effect (EPSP) on the postsynaptic cell because the binding of glutamate to these AMPA receptors will allow more positive ions into the cell. The insertion of additional AMPA receptors strengthens the synapse so that the postsynaptic neuron is more likely to fire in response to presynaptic neurotransmitter release. Some drugs co-opt the LTP pathway; this synaptic strengthening can lead to addiction.

    Long-term Depression (LTD)

    Long-term depression (LTD) is essentially the reverse of LTP: it is a long-term weakening of a synaptic connection. One mechanism known to cause LTD also involves AMPA receptors. In this situation, calcium that enters through NMDA receptors initiates a different signaling cascade, which results in the removal of AMPA receptors from the postsynaptic membrane. With the decrease in AMPA receptors in the membrane, the postsynaptic neuron is less responsive to the glutamate released from the presynaptic neuron. While it may seem counterintuitive, LTD may be just as important for learning and memory as LTP. The weakening and pruning of unused synapses trims unimportant connections, leaving only the salient connections strengthened by long-term potentiation.

    Key Points

    • Short-term synaptic enhancement occurs when the amount of available neurotransmitter is increased, while short-term synaptic depression occurs when the amount of vesicles with neurotransmitters is decreased.
    • Synapses are strengthened in long-term potentiation (LTP) when AMPA receptors (which bind to negatively-charged glutamate) are increased, allowing more calcium ions to enter the cell, causing a higher excitatory response.
    • Long-term depression (LTD) occurs when the AMPA receptors are decreased, which decreases the amount of calcium ions entering the cell, weakening the synaptic response to the release of neurotransmitters.
    • The strengthening and weakening of synapses over time controls learning and memory in the brain.

    Key Terms

    • long-term potentiation: a long-lasting (hours in vitro, weeks to months in vivo) increase, typically in amplitude, of the response of a postsynaptic neuron to a particular pattern of stimuli from a presynaptic neuron
    • long-term depression: a long-term weakening of a synaptic connection
    • plasticity: the property of neuron that allows it to be strengthened or weakened

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